Abstract 19338: Sustained Release of Endothelial Progenitor Cell Derived Exosomes From Shear-Thinning Hydrogel Improves Angiogenesis and Promotes Function After Myocardial Infarction
Introduction: Previous studies showed that administration of endothelial progenitor cells (EPCs) into ischemic myocardium improved cardiac function after myocardial infarction (MI). A growing body of literature supports the therapeutic benefit to be mediated by paracrine effectors, including cell-derived exosomes.
Hypothesis: We hypothesized that the delivery of EPC-derived exosomes within a shear-thinning gel (STG) would reproduce the beneficial effects of EPC treatment, augmenting angiogenic activity and stabilizing the infarct to decrease adverse remodeling.
Methods: Exosomes were harvested from EPCs isolated from adult male Wistar rats and characterized by electron microscopy, nanoparticle tracking analysis, and mass spectrometry. Exosomes were incorporated into the STG and injected at the border zone in rat models of MI. Hemodynamic function, angiogenesis, and myocardial remodeling were analyzed in 5 groups: phosphate buffered saline (PBS) control, STG control, exosomes in PBS, exosomes in STG, and EPCs in STG.
Results: Electron microscopy and nanoparticle tracking analysis of exosomes showed lipid bilayer-bound particles of 50-200 nm. Exosome content analysis revealed several key angiogenic factors. Exosome uptake by endothelial cells was confirmed followed by subsequent robust therapeutic angiogenesis. In vivo animal experiments demonstrated that delivery of exosomes within STG resulted in increased peri-infarct vascular proliferation and hemodynamic function post-MI (cardiac output, stroke volume, maximum pressure, ejection fraction, contractility, and ventricular compliance), which was comparable to EPC delivery in STG.
Conclusions: EPC-derived exosomes delivered into ischemic myocardium via an injectable hydrogel enhanced peri-infarct angiogenesis and myocardial hemodynamics in a rat model of MI. The STG greatly increased therapeutic efficiency and efficacy of exosome-mediated myocardial preservation.
Author Disclosures: C.W. Chen: None. C.M. Venkataraman: None. L.L. Wang: None. G. Hung: None. A.C. Gaffey: None. J.J. Chung: None. A. Liccardi: None. A. Trubelja: None. S.H. Seeholzer: None. J.A. Burdick: None. P. Atluri: None.
- © 2016 by American Heart Association, Inc.